A Double-Blind, Placebo-Controlled Study of Dronabinol in Trichotillomania and Other Body Focused Repetitive Behaviors

Pathological hair-pulling, trichotillomania, has been defined as repetitive, intentionally performed pulling that causes noticeable hair loss and results in clinically significant distress or functional impairment. Although discussed in the medical literature for over one hundred years, and affecting all strata of society, there have been no epidemiological studies detailing how common trichotillomania is and there are no clear treatment approaches for everyone with trichotillomania. Behavioral therapy is generally regarded as the first-line treatment but trained therapists are difficult to find. In addition, there is no medication currently approved by the Food and Drug Administration for trichotillomania. Trichotillomania is related clinically to other BFRBs, specifically skin picking disorder. In fact, it appears that trichotillomania and skin picking disorder may in fact share a common neurobiology. Other BFRBs such as skin ppicking disorder also lack any agreed upon medication intervention, but evidence suggests that both skin picking disorder and trichotillomania may respond to the same interventions.

The Trichotillomania Impact Project survey showed that only 15% of adults in the community with trichotillomania reported experiencing significant improvement with treatment of their symptoms. This may be because of the ongoing difficulty of finding a therapist experienced in trichotillomania treatments. More than 55% of persons in this survey believed that their clinician did not have sufficient knowledge of the disorder, and less than one-third were receiving evidence-based treatments for trichotillomania.

A recent meta-analytic study of randomized treatment trials in adults demonstrated that behavioral treatments, mainly habit reversal therapy, have the greatest efficacy in treatment of trichotillomania. Selective serotonin reuptake inhibitors (SSRIs) are the most widely used treatment for adults with trichotillomania, despite evidence that their efficacy is no greater than placebo.

Instead of using SSRIs, the investigators conducted an open-label study of dronabinol a synthetic form of tetrahydrocannabinol (THC) approved by the FDA as an appetite stimulant for people with AIDS and antiemetic for people receiving chemotherapy, in 14 women with trichotillomania and found that 9 (64.3%) responded to treatment and that the mean effective dose was 11.6 ± 4.1 mg/day.

A recent study using diffusion tensor imaging demonstrated that both trichotillomania and skin-picking subjects exhibited significantly reduced fractional anisotropy in anterior cingulate, presupplementary motor area, and temporal cortices. These data suggest that the disorganization of white matter tracts in motor habit generation and suppression may underlie the pathophysiology of these disorders. Neurochemically, motor habits may rely partially on the endocannabinoid system. CB1 receptors are highly expressed in the basal ganglia nuclei, the hippocampus, cerebellum, and neocortex and are implicated in attenuating glutamatergic exocitotoxic damage by suppressing the neuronal release of glutamate via inhibition of calcium channels. The activation of CB1 receptors reduces glutamate release in the dorsal and ventral striatum [possibly through an interaction with brain-derived neurotrophic factor], thereby modulating neurotransmission in the basal ganglia and mesolimbic reward system . Stress-induced anxious behavior has been associated with the loss of CB1 receptor function in the striatum.